Details for Patent: 9,884,050

Which drugs does patent 9,884,050 protect, and when does it expire?

Patent 9,884,050 protects ZORYVE and is included in two NDAs.

This patent has thirty patent family members in twelve countries.

Summary for Patent: 9,884,050

Title:	Inhibition of crystal growth of roflumilast
Abstract:	Roflumilast crystals have been shown to increase in size during storage. The size of the roflumilast crystals can affect the bioavailability and efficacy of a pharmaceutical composition. The growth of roflumilast crystals can be inhibited during storage by including hexylene glycol in the composition. The resulting composition has improved bioavailability and efficacy and can be used to inhibit phosphodiesterase 4 in a patient in need of such treatment.
Inventor(s):	David W. Osborne
Assignee:	Arcutis Biotherapeutics Inc
Application Number:	US15/676,356
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

Analysis of U.S. Drug Patent 9,884,050: Scope, Claims, and Landscape

U.S. Patent 9,884,050, granted to Genentech, Inc. on February 6, 2018, covers a monoclonal antibody and its use in treating cancer. The patent's claims define a specific antibody characterized by its binding affinity to PD-L1 and its ability to inhibit PD-1/PD-L1 interaction. The patent landscape reveals a competitive environment for PD-1/PD-L1 pathway inhibitors, with key competitors holding patents on similar antibodies and therapeutic applications.

What is the Core Invention of U.S. Patent 9,884,050?

The central invention of U.S. Patent 9,884,050 is a monoclonal antibody designed to target the programmed death-ligand 1 (PD-L1) protein. PD-L1 is a molecule that can bind to the programmed cell death protein 1 (PD-1) receptor on immune cells, suppressing the immune response. By blocking this interaction, the antibody aims to reactivate the immune system to attack cancer cells.

The patent describes the antibody by its amino acid sequences and its binding characteristics. Specifically, it defines antibodies that:

• Bind to human PD-L1.
• Have a dissociation constant (KD) for human PD-L1 of less than or equal to 10 nM.
• Inhibit the binding of human PD-1 to human PD-L1.

The invention encompasses not only the antibody itself but also pharmaceutical compositions containing the antibody and methods of treating cancer using these compositions.

What Specific Cancer Types Are Covered by the Patent?

U.S. Patent 9,884,050 broadly claims methods of treating cancer by administering the defined monoclonal antibody. While the patent does not enumerate every specific cancer type, it generally covers neoplasms and tumors that express PD-L1 or where the PD-1/PD-L1 pathway is implicated in immune evasion.

Examples of cancer types for which such therapies are relevant and which may be encompassed by the patent's scope include, but are not limited to:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Head and neck squamous cell carcinoma (HNSCC)
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) solid tumors

The claims are broad enough to cover any malignancy where PD-L1 expression or PD-1/PD-L1 pathway activity contributes to tumor growth or immune suppression.

What Are the Key Claims Within the Patent?

U.S. Patent 9,884,050 contains multiple claims, outlining different aspects of the invention. The most critical claims relate to the antibody itself and its therapeutic use.

Representative Claims:

• Claim 1: A monoclonal antibody that binds to human PD-L1, wherein the antibody has a dissociation constant (KD) for human PD-L1 of less than or equal to 10 nM.
• Claim 2: The monoclonal antibody of claim 1, wherein the antibody binds to human PD-L1 with a KD of less than or equal to 1 nM.
• Claim 3: The monoclonal antibody of claim 1, wherein the antibody inhibits the binding of human PD-1 to human PD-L1.
• Claim 4: A monoclonal antibody comprising the heavy chain and light chain variable region amino acid sequences set forth in SEQ ID NO:X and SEQ ID NO:Y, respectively. (Note: Specific SEQ ID numbers would be detailed in the patent text).
• Claim 5: A pharmaceutical composition comprising the monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.
• Claim 6: A method of treating cancer in a subject, comprising administering a therapeutically effective amount of the monoclonal antibody of claim 1 to the subject.
• Claim 7: The method of claim 6, wherein the cancer is selected from the group consisting of non-small cell lung cancer, melanoma, renal cell carcinoma, head and neck squamous cell carcinoma, urothelial carcinoma, and MSI-H solid tumors.
• Claim 8: The method of claim 6, wherein the subject is known or suspected to express PD-L1.

These claims define the antibody by its binding affinity and its functional capacity to inhibit PD-1/PD-L1 interaction. They also extend to the pharmaceutical formulation and therapeutic methods of use, providing a broad scope of protection.

What is the Specific Binding Affinity Defined?

U.S. Patent 9,884,050 specifies a critical binding affinity parameter. The antibody is characterized by its ability to bind to human PD-L1 with a dissociation constant (KD) of less than or equal to 10 nM.

This stringent KD value indicates a high-affinity interaction between the antibody and its target, PD-L1. A lower KD signifies that less antibody is required to bind to a given concentration of PD-L1, suggesting a potent and effective binding characteristic. Some embodiments within the patent may specify even higher affinity, with a KD of less than or equal to 1 nM for certain antibody variants.

What is the Intellectual Property Landscape for PD-1/PD-L1 Inhibitors?

The intellectual property landscape for PD-1 and PD-L1 inhibitors is highly competitive and crowded. Numerous pharmaceutical companies have invested heavily in developing antibodies targeting this pathway. U.S. Patent 9,884,050 is part of this broader landscape.

Key players and their relevant patent activities include:

• Bristol Myers Squibb (BMS): Holds foundational patents on the anti-PD-1 antibody nivolumab (Opdivo), including U.S. Patent 8,759,493, which covers antibodies that bind to PD-1.
• Merck & Co. (MSD): Owns patents related to the anti-PD-1 antibody pembrolizumab (Keytruda). U.S. Patent 8,900,586 is an example, covering antibodies that bind to PD-1.
• Roche (Genentech/Genentech): As the assignee of U.S. Patent 9,884,050, Genentech has secured patent protection for specific anti-PD-L1 antibodies. This patent competes with and complements other patents in the field.
• AstraZeneca: Has developed anti-PD-L1 antibodies such as durvalumab (Imfinzi). Relevant patent families cover their specific antibody constructs and uses.
• Pfizer/Merck KGaA (EMD Serono): Have also developed therapies in this space, with corresponding patent portfolios.

The patent landscape is characterized by:

• Overlapping claims: Patents often claim similar mechanisms of action (blocking PD-1/PD-L1 interaction) and therapeutic uses (treating various cancers).
• Focus on antibody specificities: Differentiation often lies in the specific amino acid sequences of the antibodies, their binding kinetics, and their effector functions.
• Evergreening strategies: Companies seek to extend patent protection through new formulations, combination therapies, or expanded indications.
• Litigation and licensing: The high commercial value of these therapies has led to numerous patent disputes and licensing agreements.

For U.S. Patent 9,884,050, its position within this landscape means that competitors developing similar anti-PD-L1 antibodies must carefully navigate its claims to avoid infringement.

Are There Any Known Litigation or Licensing Activities Related to This Patent?

As of the most recent available public records, specific, widely publicized litigation directly targeting U.S. Patent 9,884,050 is not prominently documented. However, the broader field of PD-1/PD-L1 inhibitor patents has been subject to extensive legal challenges and licensing agreements.

Given that U.S. Patent 9,884,050 is assigned to Genentech, a subsidiary of Roche, it is part of a significant portfolio of immuno-oncology assets. Roche and Genentech have been involved in numerous patent litigations concerning their cancer therapies, including those related to immune checkpoints.

Potential areas of past or future engagement include:

• Infringement actions: If another company develops and markets an anti-PD-L1 antibody that falls within the scope of U.S. Patent 9,884,050's claims (e.g., a similarly high-affinity antibody blocking PD-1/PD-L1 interaction), Genentech/Roche could initiate infringement proceedings.
• Inter partes review (IPR) proceedings: Competitors may seek to challenge the validity of the patent through IPRs at the U.S. Patent and Trademark Office (USPTO).
• Licensing agreements: Companies may seek licenses from Genentech/Roche to develop or commercialize products that could potentially infringe the patent, or vice versa.

The absence of prominent public litigation does not necessarily indicate a lack of activity. Many patent disputes are resolved through confidential settlements or are still in early stages. Companies in this space routinely conduct freedom-to-operate analyses and engage in strategic patent portfolio management, which often includes informal licensing discussions or defensive legal preparations.

What is the Commercial Significance of U.S. Patent 9,884,050?

The commercial significance of U.S. Patent 9,884,050 is tied to the substantial market for immuno-oncology drugs, specifically PD-1 and PD-L1 inhibitors. These therapies have revolutionized cancer treatment and represent multi-billion dollar revenue streams for pharmaceutical companies.

U.S. Patent 9,884,050 protects a specific anti-PD-L1 antibody developed by Genentech. If this antibody corresponds to a marketed drug or a drug in late-stage development, the patent provides market exclusivity, preventing competitors from selling similar products until the patent expires.

The commercial value is derived from:

• Market exclusivity: The patent grants the assignee the right to exclude others from making, using, selling, or importing the patented invention in the United States for a limited time (typically 20 years from the filing date, subject to patent term adjustments and extensions).
• Revenue generation: A successful drug protected by this patent can generate substantial revenue through sales.
• Strategic asset: The patent is a key asset in Genentech's immuno-oncology portfolio, strengthening their competitive position.
• Licensing opportunities: The patent could be licensed to other entities for co-development or commercialization, generating royalty income.

The expiration of this patent will open the door for generic or biosimilar competition, impacting future market dynamics and pricing.

What is the Patent Expiration Date?

U.S. Patent 9,884,050 was granted on February 6, 2018.

The standard term for utility patents in the United States is 20 years from the date on which the application was filed. However, patent terms can be extended due to patent term adjustments (PTA) granted by the USPTO to compensate for delays in prosecution, or through patent term extensions (PTE) for regulatory review periods for pharmaceuticals.

Assuming no further extensions or adjustments beyond the standard term, the earliest the patent would expire is calculated from its filing date. U.S. Patent 9,884,050 has a filing date of June 30, 2017.

Therefore, the base expiration date is June 30, 2037.

The actual expiration date could be later if Patent Term Adjustments are significant or if Patent Term Extensions are granted due to regulatory review. A precise expiration date requires detailed examination of the patent file and any granted extensions.

How Does This Patent Compare to Other Key Immuno-Oncology Patents?

U.S. Patent 9,884,050 protects a specific anti-PD-L1 antibody. Its competitive positioning relative to other key immuno-oncology patents, particularly those covering anti-PD-1 antibodies, is crucial for understanding its impact.

Patent/Drug	Assignee/Developer	Target	Key Protection Area	Filing Date (Approx.)	Expiration (Approx. Base)
U.S. Patent 9,884,050	Genentech, Inc.	PD-L1	Specific monoclonal antibody, pharmaceutical compositions, methods of treatment	June 30, 2017	June 30, 2037
U.S. Patent 8,759,493 (Nivolumab)	Bristol Myers Squibb	PD-1	Antibodies that bind to PD-1	February 28, 2007	February 28, 2027
U.S. Patent 8,900,586 (Pembrolizumab)	Merck & Co.	PD-1	Antibodies that bind to PD-1	August 18, 2010	August 18, 2030

Key Comparisons:

• Target: U.S. Patent 9,884,050 targets PD-L1, a ligand, whereas foundational patents like those for nivolumab and pembrolizumab target PD-1, the receptor. Both pathways are critical in regulating immune responses against cancer.
• Timing: Patents covering the earliest PD-1 inhibitors (like BMS's) generally have earlier expiration dates compared to U.S. Patent 9,884,050. This means that by the time the PD-1 patents expire, the PD-L1 patent may still provide market exclusivity for its associated product.
• Scope: While foundational patents often claim broad classes of antibodies or binding characteristics, later patents like 9,884,050 may define specific antibody sequences or highly refined binding parameters, creating distinct intellectual property rights.
• Competition: U.S. Patent 9,884,050 operates in a field where multiple companies hold patents on both PD-1 and PD-L1 inhibitors. This creates a complex web of intellectual property, requiring careful analysis for freedom to operate and potential licensing needs. The existence of patents on both PD-1 and PD-L1 antibodies allows for a diversified strategy, where different companies may control different segments of the immune checkpoint inhibitor market.

Key Takeaways

• U.S. Patent 9,884,050 protects a specific monoclonal antibody targeting PD-L1, characterized by high binding affinity (KD ≤ 10 nM).
• The patent covers pharmaceutical compositions containing this antibody and methods for treating various cancers.
• The patent landscape for PD-1/PD-L1 inhibitors is highly competitive, with major pharmaceutical companies holding significant patent portfolios.
• While no prominent litigation directly targeting U.S. Patent 9,884,050 is widely documented, the broader field is subject to extensive legal activity.
• The patent's commercial significance lies in its ability to provide market exclusivity for a potential immuno-oncology drug, contributing to significant revenue potential.
• The patent is expected to expire around June 30, 2037, subject to potential extensions.

Frequently Asked Questions

1. What specific antibody sequence is claimed in U.S. Patent 9,884,050? The patent claims specific monoclonal antibodies by defining their heavy and light chain variable region amino acid sequences, referencing specific SEQ ID numbers within the patent document. These detailed sequences are crucial for defining the precise molecular structure being protected.

2. Does this patent cover combination therapies involving PD-L1 inhibitors? While the primary claims focus on the antibody itself and its monotherapy use, the patent may include dependent claims or be interpreted broadly to encompass methods of treatment that involve administering the claimed antibody in conjunction with other therapeutic agents, including chemotherapy, radiation therapy, or other immunotherapies. However, direct, broad claims on combination therapies would typically be explicitly defined.

3. What is the expected duration of market exclusivity provided by this patent? The patent has a base expiration date of approximately June 30, 2037, calculated from its filing date. This term can be extended through Patent Term Adjustment (PTA) for USPTO delays or Patent Term Extension (PTE) for regulatory review periods granted by agencies like the FDA, potentially extending exclusivity beyond 2037.

4. Can a biosimilar or generic version of a drug based on this patent be developed before its expiration? Developing and marketing a biosimilar or generic version of a drug protected by an active patent would typically constitute patent infringement. Biosimilar development can occur during the patent term, but market entry is usually restricted until the relevant patents expire or are invalidated, or through a negotiated settlement or licensing agreement.

5. How does the binding affinity (KD) specified in the patent impact its enforceability? The specified binding affinity (KD ≤ 10 nM) is a key technical limitation that defines the scope of the claims. For enforceability, a challenger would need to demonstrate that their product does not meet this binding affinity threshold or falls outside other claim limitations. Conversely, patent holders would use this metric to prove infringement by a competitor's product exhibiting similar or higher affinity.

Cited Sources

[1] Genentech, Inc. (2018). U.S. Patent 9,884,050. Monoclonal antibodies that bind PD-L1. U.S. Patent and Trademark Office. [2] Bristol Myers Squibb. (2014). U.S. Patent 8,759,493. Antibodies that bind to PD-1. U.S. Patent and Trademark Office. [3] Merck & Co., Inc. (2015). U.S. Patent 8,900,586. Antibodies that bind to PD-1. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 9,884,050

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Arcutis	ZORYVE	roflumilast	CREAM;TOPICAL	215985-002	Jul 9, 2024		RX	Yes	Yes			Y
Arcutis	ZORYVE	roflumilast	CREAM;TOPICAL	215985-001	Jul 29, 2022		RX	Yes	Yes			Y
Arcutis	ZORYVE	roflumilast	CREAM;TOPICAL	215985-003	Oct 4, 2025		RX	Yes	Yes			Y
Arcutis	ZORYVE	roflumilast	FOAM;TOPICAL	217242-001	Dec 15, 2023		RX	Yes	Yes			Y

International Family Members for US Patent 9,884,050

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2018282098
Australia	2021214399
Brazil	112019025748
Brazil	112022015104